The lining of blood vessels, called the endothelium, is capable of secreting substances which allow blood vessels to relax in response to a variety of stimuli. One factor released is known as endothelium-derived relaxant factor (EDRF). Acetylcholine is able to promote release of EDRF from blood vessels. Absence or malfunction of the endothelium can lead to diminished dilation or vasoconstriction with acetylcholine. Little information is available on the role of EDRF in small blood vessels of the heart in patients with chest pain and normal large coronary arteries. We studied patients with normal epicardial coronary arteries who had chest pain, and on atrial pacing had reduced vasodilation. These patients also had a reduced endothelial-dependent vasodilation to acetylcholine infusions given in the coronary arteries. However, they had normal reaction to nitroprusside, an endothelial-independent vasodilator. Thus, patients with impaired flow response to atrial pacing also have a reduced response to endothelial-dependent vasodilation, but not to a vasodilator which is not dependent on intact endothelium. These results suggest that patients with microvascular angina (chest pain and normal coronary arteries) who have impaired vasodilator reserve, may also have an endothelial abnormality in the small vessels of their coronary arteries.